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InotropesEffectsα vasoC, minor inotrope incr SBPβ1 +ive inotrope and chronotrope incr SBP and COβ2 inotrope and chronotrope, vasoD in muscles decr PVR, decr DBPD1 vasoD inc renal and splanchnic bed decr peri resistanceD2 suppress NE releaseIn shock, decr endogenous NA stores and downregulation of beta-receptors, so alpha receptors become more important; may need high doses in refractory shockEpinephrineMOA: α+++ (effects incr with incr dose); β1++++ = β2+++ vasoC (counterbalanced by β effects; effect diminishes over time improved myocardium blood flow during resus) variable effect on DBP, incr SVR ino, chrono (stimulates spontaneous contractions incr defib success) incr HR Incr COIndication: in LA to decr blood flow; complete HB (if atropine and transcutaneous pacing fail); septic shock; cardiac arrest; anaphylaxis; asthma; cardiogenic shockDose: 0.1 – 2mcg/kg/min or 1-20mcg/min or 0.3 - 3mg/hr 1mg in 1L = 1mcg/ml Cardiac arrest: 1mg Q3mins Anaphylaxis: IM: 1:1000; Adult: 0.3-0.5ml (Children: 0.01ml/kg); Repeat Q5-15min IV: 1:100,000 max concentration 100 - 200mcg (1.5-3mcg/kg) slow IV bolus 0.1 - 1mcg/kg/min infusion NEB: 5ml (0.5ml/kg) 1:1000 Onset: 1-3 minsDOA: 2-10minsPros: 10% less arrhythmia than dopamineCons: ICH, HTN, arrhythmia, local ischaemia, anxiety, incr myocardial O2 consumption (negative effect on survival in post-resus state); in prolonged cardiac arrest, metabolic acidosis decr efficacy; tachyphylaxis; hyperG; lactic acidosis; needs CVL; decr renal/pul/splanchnic flowCI: IHD, HTN, hyperthyroid, phaeochormocytoma, glaucomaInteractions: incr responsiveness with TCA’s and MAOI’sStudies: high vs low dose = better ROSC with high dose, but no difference in survivalNorepinephrineMOA: α++++ (effects incr with dose); β1++++ >> β2 0 vasoC (renal and mesenteric), no vasoD incr SBP and DBP, incr SVR ino and chrono incr HR incr CO at low dose, decr CO at high dose (due to incr afterload) improved renal blood flow and UO in sepsisIndication: vasoD shock (eg. anaphylaxis, septic shock); cardiogenic shock with severe hypotensionDose: 0.1 – 2mcg/kg/min or 1-20mcg/min or 0.3-3mg/hr 1mg in 1L = 1mcg/mlPros: useful when loss of venous tone as no vasoD; spares coronary circulationCons: needs CVL; decr renal/pul/splanchnic flow; decr HR at high dose may decr COSE: dose-related reflex bradycardia, V arrhythmias, irritant with extravasationDopamineMOA: D1, D2 and β2 at low dose; β1++++ at mod dose; α activated at high doses ino (indirectly increases NE release), chrono at mod dose incr HR at mod dose, decr HR at high dose vasoD (renal, mesenteric, coronary, intracerebral) at low dose decr BP at low dose vasoC inc renal bed at higher doses, reflex bradycardia incr BP and SVR at high dose incr COIndication: Anaphylaxis, hypotension, cardiogenic shock with mild hypotension, trauma, sepsis, CHBDose: 2 –50mcg/kg/min or 0.15–1.5mg/min or 10-50mg/hrHalf life: 2 minsPros: can use peripherally for short period of timeCons: depresses resp drive; intrapul shunting decr paO2; may transiently decr T cell function; tissue ischaemia with extravasation so best given via CVL (can be given peripherally short term); low dose will incr UO due to diuretic action, but does not protect against ARF; can cause arrhythmias, incr myocardial O2 consumption; tachyphylaxis at high dose; headache, N+VCI: PVD, pul HTN, ?pregnancyDobutamineMOA: β1++++ >> β2++; some α + vasoC Decr LV filling p, decr pul vasc resistance; vasoD decr afterload in low CO states decr SVR less vasoD so less reflex incr HR chrono, ino incr HR incr COIndication: anaphylaxis, mild hypotension (SBP 80-100); 1st line in CCF; cardiogenic shock, RV infarctDose: 2 – 20mcg/kg/min or 0.15–1.5mg/min or 10-50mg/hrOnset: 1-3 minsPeak: 10minsPros: can be given via peri lineCons: V ectopy at high doses; elderly patients relatively resistant; variable response in critically ill; causes arrhythmias, incr myocardial O2 consumption, hypotension if vol deplete (combine with NAD to avoid); headache, tremors, anginaPhenylephrine / metaraminolMOA: pure α agonist vasoC incr SBP mydriatic; decongestant decr COIndication: hypotension; in LA to decr blood flow; shock 2Y to tachycardia; distributive shock; useful in severe AS and HOCM as not a chronotropeDose: 100-200mcg/min or boluses phenylephrine; 1mg boluses or 1-5mg/hr INF metaraminolDOA: 20mins phenylephrineSE: reflex bradycardia, incr afterload (avoid in cardiogenic shock), headacheIsoprenalineMOA: β1++++ = β2++++; no α affect ino, chrono (incr HR), incr CO vasoDIndications: refractory bradycardia, TdPDose: 20-40mcg IV bolus 0.5-20mcg/min = 0.05-1mg/hrSE: tachyarrhythmia, facial flushing, hypotension if hypovolaemia, incr myocardial O2 consumptionCI: digitoxicityVasopressinMOA: acts via V1 on vascular SM and α peri vasoC (incr CA, cerebral and renal blood flow)Indications: occasionally in vasodilatory shock (eg. Sepsis); insufficient evidence to support use in cardiac arrest (?indicated in asystole); use in catecholamine resistant statesDose: 0.01 – 0.04iu/min in septic shock; 40iu IV in cardiac arrestSE: arrhythmia, MIStudies: no difference between vasopressin and adrenaline in cardiac arrest for ROSC, survival 24hrs, survival to discharge; one subset when used prehospital had significant incr in survival to discharge, and better results in asystole, but not neurologically intactEphedrineMOA: α and β; incr CODose: 5-25mg IV bolus to max 150mg/24hrsSE: HTN, arrhythmiasNotes from: DunnReceptorAgonistAntagonistEndogenous agonistsSite and Actionα receptorsE > NE > isopretenerolVascoC: incr arterial resistance incr BP; decr venous capacitance incr VR incr SVPositive inotropeα1 type (type 1A, B, D)Phenylephrine, methoxamine (α2 also but to lesser extent)PrazosinVasoCHeart incr contractilityMydriasis, decr IOpPilomotor SM erects hairProstate contractionα2 typeClonidine, methylnorepinephrine (α1 also, but to lesser extent) YohimbineVasoC (in skin and splanchnic)Postsynaptic CNS adrenoceptors multiplePlt aggregationAdrenergic and cholinergic nerve terminals NT releaseInhibition of lipolysisα 2AOxymetazolineα 2BPrazosinα 2CPrazosinReceptorAgonistAntagonistEndogenous agonistsSite and Actionβ receptorsIsoproterenol (β1= β2); dobutamine (β1> β2); terbutaline, metaproterenol, albuterol, ritodrine (β2>> β1)PropanololIsopretenerol > E > NEIncr COβ 1DobutamineBetaxololE = NEIncr HR and contractility – incr pacemaker activity, incr conduction velocity at AVN, decr refractory periodβ 2AlbuterolButoxamineE > NEVasoD decr peri resistanceBronchoDUterine and bladder relaxationIncr K uptake by skeletal musclesLiver glycogenolysisβ 3LipolysisReceptorAgonistAntagonistEndogenous agonistsSite and ActionDopamine receptorsDopamine (D1=D2); fenoldopam (D1>>D2)Important in brain, splanchnic and renal vasculatureD1FenoldopamRenal vasoDD2BromocriptineNerve endings modulates NT releaseD3D4ClozapineD5 ................
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